Faculty Bibliography

BACKGROUND:Exposure to bisphenols and phthalates in pregnancy may lead to adverse health effects in women themselves and their offspring. OBJECTIVE:To describe first trimester bisphenol and phthalate urine concentrations, including bisphenol and phthalate replacements, and determine nutritional, socio-demographic and lifestyle related determinants. METHODS:In a population-based prospective cohort of 1396 mothers, we measured first trimester bisphenol, phthalate and creatinine urine concentrations (samples collected in 2004-2005, median gestational age 12.9 weeks [inter-quartile range (IQR) 12.1-14.4]). We examined associations of potential determinants with log-transformed bisphenol and phthalate concentrations. Outcomes were back-transformed. Nutritional analyses were performed in a subgroup of 642 Dutch participants only, as the Food Frequency Questionnaire was aimed at Dutch food patterns. RESULTS:Bisphenol A, bisphenol S, and bisphenol F were detected in 79.2%, 67.8% and 40.2% of the population, respectively. Mono-n-butylphthalate, mono-(2-ethyl-5-hydroxyhexyl)phthalate and monobenzylphthalate were detected in > 90% of the population. Nutritional intake was not associated with bisphenol and phthalate concentrations after correction for multiple testing was applied. Obesity was associated with higher high-molecular-weight phthalate concentrations and the lack of folic acid supplement use with higher di-n-octylphthalate concentrations (respective mean differences were 46.73nmol/l [95% CI 14.56-93.72] and 1.03nmol/l [0.31-2.06]). CONCLUSION/CONCLUSIONS:Bisphenol S and F exposure was highly prevalent in pregnant women in the Netherlands as early as 2004-5. Although associations of dietary and other key factors with bisphenol and phthalate concentrations were limited, adverse lifestyle factors including obesity and the lack of folic acid supplement use seem to be associated with higher phthalate concentrations in pregnant women. The major limitation was the availability of only one urine sample per participant. However, since phthalates are reported to be quite stable over time, results concerning determinants of phthalate concentrations are expected to be robust.

BACKGROUND AND OBJECTIVE: In utero exposure to perfluorooctanoic acid (PFOA) has been associated with decreases in birth weight. We aimed to estimate the proportion of PFOA-attributable low birth weight (LBW) births and associated costs in the US from 2003 to 2014, a period during which there were industry-initiated and regulatory activities aimed at reducing exposure. METHODS: Serum PFOA levels among women 18-49 years were obtained from the National Health and Nutrition Examination Survey (NHANES) for 2003-2014; birth weight distributions were obtained from the Vital Statistics Natality Birth Data. The exposure-response relationship identified in a previous meta-analysis (18.9g decrease in birth weight per 1ng/mL of PFOA) was applied to quantify PFOA-attributable LBW (reference level of 3.1ng/mL for our base case, 1 and 3.9ng/mL for sensitivity analyses). Hospitalization costs and lost economic productivity were also estimated. RESULTS: Serum PFOA levels remained approximately constant from 2003-2004 (median: 3.3ng/mL) to 2007-2008 (3.5ng/mL), and declined from 2009-2010 (2.8ng/mL) to 2013-2014 (1.6ng/mL). In 2003-2004, an estimated 12,764 LBW cases (4% of total for those years) were potentially preventable if PFOA exposure were reduced to the base case reference level (10,203 cases in 2009-2010 and 1,491 in 2013-2014). The total cost of PFOA-attributable LBW for 2003 through 2014 was estimated at $13.7 billion, with $2.97 billion in 2003-2004, $2.4 billion in 2009-2010 and $347 million in 2013-2014. CONCLUSIONS: Serum PFOA levels began to decline in women of childbearing age in 2009-2010. Declines were of a magnitude expected to meaningfully reduce the estimated incidence of PFOA-attributable LBW and associated costs.

BACKGROUND AND OBJECTIVE: Few studies have examined the possible cardiometabolic consequences of World Trade Center-related exposures on children who lived and/or attended school near the disaster site. Our objective was to compare cardiometabolic profiles of participants in the World Trade Center Health Registry (WTCHR) with a matched comparison group. METHODS: We evaluated WTCHR enrollees who resided in New York City and were born between September 11, 1993 and September 10, 2001, and a matched comparison group. We assessed exposure to dust cloud, home dust, as well as traumatic exposure, and associations with blood pressure, arterial wall stiffness, body mass index (BMI), total cholesterol, triglycerides, HDL, and LDL. RESULTS: A total of 402 participants completed the study, 222 in the comparison group and 180 in the WTCHR group. In multivariable regression analysis, after adjusting for relevant confounders we detected a weak association between participation in the WTCHR group and lower BMI (-1.12kg/m2, 95% CI -2.11, -0.12; p = 0.03), which became non-significant after adjusting for multiple comparisons. With respect to traumatic and psychosocial exposures, the only association that persisted in our multivariable model, below our predefined level of significance, was between post-traumatic stress disorder and higher BMI (2.06kg/m2, 95% CI 0.37, 3.74; p = 0.02). CONCLUSIONS: Our findings do not support an association between self-reported exposures to the WTC disaster and adverse cardiometabolic profile. However, further longitudinal studies may better inform the full extent of WTC-related conditions associated with exposure to the disaster.

Adequate docosahexaenoic acid (DHA) is essential for the optimal growth and development of the fetus. Maternal DHA content fluctuates during pregnancy. The correlation of DHA content with dietary intake might be varied over the course of pregnancy. We aimed to compare the dietary DHA intake, estimated by a DHA-specific semiquantitative food frequency questionnaire (FFQ) against its blood content, among mid- and late-term pregnant women. A total of 804 Chinese pregnant women completed the tailored FFQ and provided fasting venous blood samples. Dietary DHA intake (mg/day) in the previous month was calculated from the FFQ using Chinese Food Composition Table. DHA concentrations (weight percent of total fatty acids) in plasma and erythrocytes were measured by capillary gas chromatography. Spearman correlation coefficients (r_s) between DHA intake and its relative concentrations were calculated. After adjustment for maternal age, pre-pregnancy body mass index, stage of pregnancy, parity, education level, ethnicity, and annual family income per capita, the correlation coefficients of DHA intake with its concentrations in plasma and erythrocytes were 0.35 and 0.33, respectively (p < 0.001). The correlations were relatively stronger among women in late pregnancy (r_s = 0.44 in plasma and 0.39 in erythrocytes) than those in mid-pregnancy (r_s = 0.25 and 0.26). The significant correlations were consistently observed in subgroups stratified by regions, except for erythrocytes in women living in a coastland area. Multiple regression analyses also indicated significant positive linear correlations between DHA intake and its plasma or erythrocytes concentrations (p < 0.001). In conclusion, dietary DHA intake, estimated by the FFQ, was positively correlated with its concentrations in plasma and erythrocytes in Chinese pregnant women, especially for women in late pregnancy, with the exception of the erythrocytes of those living in a coastland area.

Using a population-based birth cohort in upstate New York (2008-2010), we examined the determinants of brain-derived neurotrophic factor (BDNF) measured in newborn dried blood spots (n = 2,637). We also examined the association between neonatal BDNF and children's development. The cohort was initially designed to examine the influence of infertility treatment on child development but found no impact. Mothers rated children's development in five domains repeatedly through age 3 years. Socioeconomic and maternal lifestyle determinants of BDNF were examined using multivariable linear regression models. Generalized linear mixed models estimated odds ratios for neonatal BDNF in relation to failing a developmental domain. Smoking and drinking in pregnancy, nulliparity, non-White ethnicity/race, and prepregnancy obesity were associated with lower neonatal BDNF. Neonatal BDNF was not associated with failure for developmental domains; however, there was an interaction between BDNF and preterm birth. In preterm infants, a higher BDNF was associated with lower odds of failing any developmental domains, after adjusting for confounders and infertility treatment. This result was particularly significant for failure in communication. Our findings suggest that BDNF levels in neonates may be impacted by maternal lifestyle characteristics. More specifically, lower neonatal BDNF might be an early marker of aberrant neurodevelopment in preterm infants.

Children raised in economically disadvantaged households face increased risks of poor health in adulthood, suggesting that inequalities in health have early origins. From the child's perspective, exposure to economic hardship may begin as early as conception, potentially via maternal neuroendocrine-immune responses to prenatal stressors, which adversely impact neurodevelopment. Here we investigate whether socioeconomic disadvantage is associated with gestational immune activity and whether such activity is associated with abnormalities among offspring during infancy. We analyzed concentrations of five immune markers (IL-1β, IL-6, IL-8, IL-10, and TNF-α) in maternal serum from 1,494 participants in the New England Family Study in relation to the level of maternal socioeconomic disadvantage and their involvement in offspring neurologic abnormalities at 4 mo and 1 y of age. Median concentrations of IL-8 were lower in the most disadvantaged pregnancies [-1.53 log(pg/mL); 95% CI: -1.81, -1.25]. Offspring of these pregnancies had significantly higher risk of neurologic abnormalities at 4 mo [odds ratio (OR) = 4.61; CI = 2.84, 7.48] and 1 y (OR = 2.05; CI = 1.08, 3.90). This higher risk was accounted for in part by fetal exposure to lower maternal IL-8, which also predicted higher risks of neurologic abnormalities at 4 mo (OR = 7.67; CI = 4.05, 14.49) and 1 y (OR = 2.92; CI = 1.46, 5.87). Findings support the role of maternal immune activity in fetal neurodevelopment, exacerbated in part by socioeconomic disadvantage. This finding reveals a potential pathophysiologic pathway involved in the intergenerational transmission of socioeconomic inequalities in health.

BACKGROUND:Maternal retinol-binding protein 4 (RBP4) and lipids may relate to preeclampsia and preterm birth risk but longitudinal data are lacking. This study examines these biomarkers longitudinally during pregnancy in relation to preeclampsia and preterm birth risk. METHODS:Maternal serum samples from the Calcium for Preeclampsia Prevention (CPEP) trial were analyzed at baseline: average 15 gestational weeks; mid-pregnancy: average 27 weeks; and at >34 weeks. We measured RBP4, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides and lipoprotein (a) (Lp(a)). Cross-sectional logistic regression analyses estimated the odds ratio (OR) and 95% confidence intervals (CI) for preterm preeclampsia (n = 63), term preeclampsia (n = 104), and preterm delivery (n = 160) associated with RBP4 and lipids at baseline and mid-pregnancy compared with controls (n = 136). Longitudinal trajectories across pregnancy were assessed using mixed linear models with fixed effects. Adjusted models included clinical and demographic factors. RESULTS:RBP4 concentrations at baseline and mid-pregnancy were associated with a 4- to 8-fold increase in preterm preeclampsia risk but were not associated with term preeclampsia. RBP4 measured mid-pregnancy was also associated with preterm birth (OR = 6.67, 95% CI: 1.65, 26.84). Higher triglyceride concentrations in mid-pregnancy were associated with a 2- to 4-fold increased risk for both preeclampsia and preterm birth. Longitudinal models demonstrate that both preterm preeclampsia and preterm birth cases had elevated RBP4 throughout gestation. CONCLUSIONS:Elevated RBP4 is detectable early in pregnancy and its strong relation with preterm preeclampsia merits further investigation and confirmation to evaluate its potential use as a predictor, particularly among high-risk women.